73 The In Vitro Control of Calcification in Osteogenesis Imperfecta

Abstract

Previous work has implicated bone collagen obtained from patients with osteogenesis imperfecta as a potent inhibitor of the in vitro formation of bone mineral. The present investigation further examines the mechanism of inhibition and suggests a possibility for therapy. It was observed that the citrate-soluble fraction of bone collagen from two patients with the disease had a pyrophosphate content of 1.4 μm/mg collagen which is four times the normal value. Urinary excretion of pyrophosphate was also elevated. As pyrophosphates are thought to be inhibitors of calcification both in vitro and in vivo (FLEISCH, H. et al. Nature 212: 903-3 [1966].), the abnormal collagen was treated with the enzyme pyrophosphatase in the presence of Mg as cofactor during the in vitro mineralization procedure. It was found that Mg alone significantly increased the catalytic properties of osteogenesis imperfecta collagen and this effect was doubled when pyrophosphatase was present. These results suggest that collagen-bound pyrophosphate is partly responsible for the failure of bone matrix to calcify. The possibility that these patients need a high level of Mg as cofactor for their pyrophosphatase activity is being investigated. (Supported by U.S.P.H.S. AM 08757–03) (SPR).